The utility of the urinary proteome in infectious diseases remains unclear. Here we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine but only 124 in serum using TMT-based proteomics. Decrease of urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. Downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomic analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomic analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

The relationship among the gut microbiome, global fecal metabolites and rheumatoid arthritis (RA) has not been systematically evaluated. In this study, we performed 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based nontargeted metabolomic profiling on feces of 26 untreated RA patients and 26 healthy controls. Twenty-six genera and forty-one MS2-identified metabolites were significantly altered in the RA patients. Klebsiella, Escherichia, Eisenbergiella and Flavobacterium were more abundant in the RA patients, while Fusicatenibacter, Megamonas and Enterococcus were more abundant in the healthy controls. Function prediction analysis demonstrated that the biosynthesis pathways of amino acids, such as L-arginine and aromatic amino acids, were depleted in the RA group. In the metabolome results, fecal metabolites including glycerophospholipids (PC(18:3(9Z,12Z,15Z)/16:1(9Z)), lysoPE 19:1, lysoPE 18:0, lysoPC(18:0/0:0)), sphingolipids (Cer(d18:0/16:0), Cer(d18:0/12:0), Cer(d18:0/14:0)), kynurenic acid, xanthurenic acid and 3-hydroxyanthranilic acid were remarkably altered between the RA patients and healthy controls. Dysregulation of pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism and glycerophospholipid metabolism, may contribute to the development of RA. Additionally, we revealed that the gut microbiome and metabolites were interrelated in the RA patients, while Escherichia was the core genus. By depicting the overall landscape of the intestinal microbiome and metabolome in RA patients, our study could provide possible novel research directions regarding RA pathogenesis and targeted therapy.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer in the world. To comprehensively investigate the utility of microRNAs (miRNAs) and protein-encoding transcripts (messenger RNAs [mRNAs]) in HCC as potential biomarkers for early detection and diagnosis, we exhaustively mined genomic data from three available omics datasets (GEO, Oncomine, and TCGA), analyzed the overlaps among gene expression studies from 920 hepatocellular carcinoma samples and 508 healthy (or adjacent normal) liver tissue samples available from six laboratories, and identified 178 differentially expressed genes (DEGs) associated with HCC. Paired with miRNA and lncRNA data, we identified 23 core genes that were targeted by nine differentially expressed miRNAs and 21 HCC-specific lncRNAs. We further demonstrated that alterations in these 23 genes were quite frequent, with five genes altered in over 5% of the population. Patients with high levels of YWHAZ, ENAH, and HMGN4 tended to have high-grade tumors and shorter overall survival, suggesting that these genes could be promising candidate biomarkers for disease and poor prognosis in patients with HCC. Our comprehensive mRNA, miRNA, and lncRNA omics analyses from multiple independent datasets identified robust molecules that may be used as biomarkers for early HCC detection and diagnosis.

Prostate cancer (PCa) is one of the most common tumors in men and can be lethal, especially if left untreated. A substantial majority of PCa patients not only are diagnosed based on fine needle aspiration (FNA) biopsies, but their treatment choices are also largely driven by the pathological findings obtained with these FNA specimens. It is widely believed that lncRNAs have strong biological significance, but their specific functions and regulatory networks have not been elucidated. LncRNAs may serve as key players and regulators of PCa carcinogenesis and could be novel biomarkers of this cancer. To identify potential markers for early detection of PCa, in this study, we employed a competing endogenous RNA (ceRNA) microarray to identify differentially expressed lncRNAs (DelncRNAs) in PCa tissue and quantitative real-time PCR (qRT-PCR) analysis to validate these DelncRNAs in FNA biopsies. We demonstrated that a total of 451 lncRNAs were differentially expressed in four pairs of PCa/adjacent tissues, and upregulation of the lncRNAs RP11-33A14.1, RP11-423H2.3, and LAMTOR5-AS1 was confirmed in FNA biopsies of PCa by qRT-PCR and was consistent with the ceRNA array data. The association between the expression of the lncRNA LAMTOR5-AS1 and aggressive cancer was also investigated. Regulatory network analysis of DelncRNAs showed that the lncRNAs RP11-33A14.1 and RP11-423H2.3 targeted miR-7, miR-24-3p, and miR-30 and interacted with the RNA binding protein FUS. Knockdown of these DelncRNAs in PCa cells also demonstrated the effects of RP11-423H2.3 on miR-7/miR-24/miR-30 or LAMTOR5-AS1 on miR-942-5p/miR-542-3p via direct interaction. The results of these studies indicate that these three specific lncRNA signatures and regulatory

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